Maculopathy and adult-onset ataxia in patients with biallelic MFSD8 variants.
CLN7
MFSD8
NCL7
ataxia
neuronal ceroid lipofuscinosis
retinal degeneration
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
Aug 2024
Aug 2024
Historique:
revised:
17
07
2024
received:
16
05
2024
accepted:
24
07
2024
medline:
7
8
2024
pubmed:
7
8
2024
entrez:
7
8
2024
Statut:
ppublish
Résumé
Biallelic variants in the major facilitator superfamily domain containing 8 gene (MFSD8) are associated with distinct clinical presentations that range from typical late-infantile neuronal ceroid lipofuscinosis type 7 (CLN7 disease) to isolated adult-onset retinal dystrophy. Classic late-infantile CLN7 disease is a severe, rare neurological disorder with an age of onset typically between 2 and 6 years, presenting with seizures and/or cognitive regression. Its clinical course is progressive, leading to premature death, and often includes visual loss due to severe retinal dystrophy. In rare cases, pathogenic variants in MFSD8 can be associated with isolated non-syndromic macular dystrophy with variable age at onset, in which the disease process predominantly or exclusively affects the cones of the macula and where there are no neurological or neuropsychiatric manifestations. Here we present longitudinal studies on four adult-onset patients who were biallelic for four MFSD8 variants. Two unrelated patients who presented with adult-onset ataxia and had macular dystrophy on examination were homozygous for a novel variant in MFSD8 NM_152778.4: c.935T>C p.(Ile312Thr). Two other patients presented in adulthood with visual symptoms, and one of these developed mild to moderate cerebellar ataxia years after the onset of visual symptoms. Our observations expand the knowledge on biallelic pathogenic MFSD8 variants and confirm that these are associated with a spectrum of more heterogeneous clinical phenotypes. In MFSD8-related disease, adult-onset recessive ataxia can be the presenting manifestation or may occur in combination with retinal dystrophy.
Sections du résumé
BACKGROUND
BACKGROUND
Biallelic variants in the major facilitator superfamily domain containing 8 gene (MFSD8) are associated with distinct clinical presentations that range from typical late-infantile neuronal ceroid lipofuscinosis type 7 (CLN7 disease) to isolated adult-onset retinal dystrophy. Classic late-infantile CLN7 disease is a severe, rare neurological disorder with an age of onset typically between 2 and 6 years, presenting with seizures and/or cognitive regression. Its clinical course is progressive, leading to premature death, and often includes visual loss due to severe retinal dystrophy. In rare cases, pathogenic variants in MFSD8 can be associated with isolated non-syndromic macular dystrophy with variable age at onset, in which the disease process predominantly or exclusively affects the cones of the macula and where there are no neurological or neuropsychiatric manifestations.
METHODS
METHODS
Here we present longitudinal studies on four adult-onset patients who were biallelic for four MFSD8 variants.
RESULTS
RESULTS
Two unrelated patients who presented with adult-onset ataxia and had macular dystrophy on examination were homozygous for a novel variant in MFSD8 NM_152778.4: c.935T>C p.(Ile312Thr). Two other patients presented in adulthood with visual symptoms, and one of these developed mild to moderate cerebellar ataxia years after the onset of visual symptoms.
CONCLUSIONS
CONCLUSIONS
Our observations expand the knowledge on biallelic pathogenic MFSD8 variants and confirm that these are associated with a spectrum of more heterogeneous clinical phenotypes. In MFSD8-related disease, adult-onset recessive ataxia can be the presenting manifestation or may occur in combination with retinal dystrophy.
Substances chimiques
MFSD8 protein, human
0
Membrane Transport Proteins
0
Types de publication
Journal Article
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2505Subventions
Organisme : Intramural research fund of FRIGE-Institute of Human Genetics
Organisme : BioMarin Pharmaceutical
Organisme : Skånes universitetssjukhus
Organisme : Region Skåne
Organisme : Stiftelsen Synfrämjandets Forskningsfond
Organisme : Ögonfonden
Organisme : National Institute for Health Research Biomedical Research Centre at University College London Great Ormond Street Institute of Child Health
Organisme : Stiftelsen Kronprinsessan Margaretas Arbetsnämnd för Synskadade
Organisme : Hans-Gabriel och Alice Trolle-Wachtmeisters stiftelse för medicinsk forskning
Organisme : Stig och Ragna Gorthons Stiftelse
Organisme : Stiftelsen för Synskadade i f.d. Malmöhus län
Organisme : Avtal för läkarutbildning och forskning (ALF)
Informations de copyright
© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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